5-Iminodaunorubicin and N,N-dibenzyldaunorubicin are analogs of adriamycin that show improved properties. These compounds are being used as the points of departure in a systematic, multidisciplinary effort to develop still better analogs. Synthesis of new analogs is integrated with in vitro tests for DNA interaction, antitumor screening in mice, metabolism studies in tissues and whole animals, and determination of cardiotoxic effects. The cardiotoxic effects are determined by measuring electrocardiographic changes in treated rats, and by comparing morphologic effects on nucleolar ultrastructure of heart, liver, and muscle cells. A specific aspect of the metabolism studies is to compare the enhancement of microsomal 02 consumption by the various analogs; the resultant generation of oxygen radicals may be related to the biologic action of the anthracyclines.